Letter to the Editor: Nonalcoholic Fatty Liver Disease Without Metabolic-Associated Fatty Liver Disease and Metabolic Syndrome
Authors: Tomoyuki Kawada
Journal: Clinical Gastroenterology and Hepatology (2022)

I read with great interest the article by Sinn et al.1Sinn D.H. et al.Clin Gastroenterol Hepatol. 2023; 21: 1873-1880.e1Abstract Full Text Full Text PDF Scopus (6) Google Scholar In this study, the authors conducted a prospective study to investigate the risk of metabolic syndrome in patients with nonalcoholic fatty liver disease (NAFLD), who were not categorized as metabolic-associated fatty liver disease (MAFLD) at baseline. The adjusted hazard ratio of patients with NAFLD and non-MAFLD for metabolic syndrome was 1.61 (95% confidence interval, 1.42–1.83). Increased waist circumference and elevated serum triglycerides level were strong predictors for incident metabolic syndrome. The authors presented the need for early intervention for patients with NAFLD and non-MAFLD to prevent metabolic syndrome, and I have 2 queries about the study. First, Younossi et al2Younossi Z.M. et al.Hepatology. 2022; 76: 1423-1437Crossref PubMed Scopus (71) Google Scholar compared the long-term outcomes of patients with NAFLD and MAFLD. They used 2 datasets, NHANES III and NHANES 2017–2018, which included patients with fatty liver disease (FLD). In NHANES 2017–2018, a total of 36.8% were classified as FLD, and proportions of NAFLD and MAFLD were 34.2% and 36.3%, respectively. Kappa coefficients between MAFLD and NAFLD diagnoses were 0.83–0.94, indicating high concordance. During long-term follow-up with median of 22.8 years, there were no significant differences in cumulative all-cause and cause-specific mortality. In contrast, the stage of fibrosis and insulin resistance were predictors of liver mortality in NAFLD, and alcohol-associated liver disease was a predictor of mortality in MAFLD. This means that specific mortality could be predicted by different independent variables in NAFLD and MAFLD, respectively. There may be a reason for establishing a new clinical concept, and different components in each disorder may contribute to different clinical outcomes, including mortality. Nevertheless, Sinn et al1Sinn D.H. et al.Clin Gastroenterol Hepatol. 2023; 21: 1873-1880.e1Abstract Full Text Full Text PDF Scopus (6) Google Scholar clarified that metabolic syndrome may be closely related to NAFLD and MAFLD even in patients with NAFLD and non-MAFLD. Triggers of incident metabolic syndrome may exist even in the NAFLD-only group. Second, van Kleef et al3van Kleef L.A. et al.Hepatology. 2022; 75: 419-429Crossref PubMed Scopus (54) Google Scholar compared the MAFLD and NAFLD criteria by using data of the Rotterdam Study. Liver ultrasound and transient elastography program were applied and participants were classified into overlap FLD, NAFLD-only, MAFLD-only, or no FLD. Among 5445 participants, 1866 (34.3%) had MAFLD and 1604 (29.5%) had NAFLD. A total of 1547 (28.4%) individuals were classified as overlap FLD, 319 (5.9%) as MAFLD-only, 57 (1.0%) as NAFLD-only, and 3522 (64.7%) as no FLD, respectively. Interestingly, they observed that the MAFLD-only group was strongly associated with fibrosis and log-transformed liver stiffness, which was not observed in the NAFLD-only group. There were discrepancies regarding risk factors of clinical outcomes in NAFLD and MAFLD, and I suspect that cause-specific morality and incidence may relate to different risk factors in NAFLD and MAFLD, which should be specified by further studies. Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic SyndromeClinical Gastroenterology and HepatologyVol. 21Issue 7PreviewMetabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. Full-Text PDF ReplyClinical Gastroenterology and HepatologyVol. 21Issue 9PreviewWe thank Dr. Kawada for the interest in our paper.1 We agree with Dr. Kawada that different risk factors of metabolic dysfunction–associated fatty liver disease (MAFLD) and nonalcoholic fatty liver disease (NAFLD) may contribute to different clinical outcomes, including mortality. By definition, in distinction from NAFLD, MAFLD does not exclude individuals with excessive alcohol consumption, or secondary causes of steatosis, such as steatogenic drug or chronic viral hepatitis B or C.2 Instead, MAFLD does exclude individuals with no or minimal metabolic dysfunction. Full-Text PDF